Conjugated polyenes is an interesting class of widely occurring natural polyketides as they have been shown to possess excellent biological properties such as antibacterial (Shim S H et al., (2011) J Nat Prod 74(3): 395-401), antifungal (Shim S H et al. supra; Chomcheon P et al., (2010) Chemistry 16(36): 11178-11185) and antitumor activities (Gross H et al. (2009) Org Lett 11(21): 5014-5017; Yang Y L et al. (2007) Chemistry 13(24): 6985-6991).
Inflammation occurs in response to numerous conditions including physical injury, irritation, tumor growth in tissue, and bacterial, parasitic, fungal, or viral infection. Inflammation causes both local and systemic effects. Representative effects that can occur at the site of injury, irritation, or disease are the increase of vascular permeability, release of degradative enzymes including metalloproteinase, migration of leukocytes to the affected site, neutrophil burst response to destroy invading cells, and the secretion of cytokines Important systemic effects include pain, fever, and the acute response in the liver.
Inflammatory cells include lymphocytes, mononuclear macrophages and dendritic cells. Once activated, these inflammatory cells can induce a series of inflammatory responses by releasing inflammatory mediators, against the infections or foreign particles. Further, nitric oxide (NO), interleukin-6 (IL-6), and TNF-α are important pro-inflammatory mediators that are produced mainly by lipopolysaccharide (LPS)-activated macrophages and mediate multiple biological effects, including the activation of immune responses. Additionally, the inflammasome is a multi-protein signal complex for activating caspase-1. Among the inflammasome, the NLRP3 inflammasome is one of the most well-studied. The NLRP3 inflammasome is activated by adenosine triphosphate in LPS-activated macrophages, leading to caspase-1 activation and IL-1β secretion (Hu Y, et al., J Immunol. 2010 Dec. 15; 185(12):7699-705).
In our previous works, we isolated certain polyketides from thermophilic fungus Myceliophthora thermophila, and demonstrated that some of these compounds exhibited antitumor activity (Yang Y L et al. supra). We also synthesized a class of polyenylpyrroles and their analogs which were evaluated for their anti-tumor activities. However, the anti-inflammation activities of the polyenylpyrrole derivatives are not disclosed.